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Gene Review

MLN  -  motilin

Homo sapiens

Synonyms: Promotilin
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Disease relevance of MLN


Psychiatry related information on MLN


High impact information on MLN

  • We studied the effects of octreotide on intestinal motility and plasma motilin concentrations in five fasting patients with scleroderma who had bacterial overgrowth and in six fasting normal subjects [6].
  • Plasma motilin concentrations, which were higher in the patients with scleroderma (229 +/- 74 pmol per liter) than in the normal subjects (112 +/- 37 pmol per liter), were inhibited by octreotide, suggesting that intestinal activity evoked by octreotide is independent of motilin [6].
  • Motilin is a 22-amino acid peptide hormone expressed throughout the gastrointestinal (GI) tract of humans and other species [7].
  • A heterotrimeric guanosine triphosphate-binding protein (G protein)-coupled receptor for motilin was isolated from human stomach, and its amino acid sequence was found to be 52 percent identical to the human receptor for growth hormone secretagogues [7].
  • Erythromycin, a motilin agonist, induces gastric emptying [8].

Chemical compound and disease context of MLN


Biological context of MLN


Anatomical context of MLN

  • Internalized MR-GFP vesicles disappeared within 15 to 45 min of motilin withdrawal but did not overlap with the lysosomal compartment, indicating that MR-GFP escaped degradation and was recycled back to the plasma membrane [18].
  • Motilin is an intestinal peptide that stimulates contraction of gut smooth muscle [19].
  • The binding of (125)I-labeled motilin to tissue membranes prepared from human stomach and duodenum was studied; rabbit tissues were used for comparison [19].
  • The aim of this study was to determine neural or muscular localization of motilin receptors in human upper gastrointestinal tract and to investigate their pharmacological characteristics [19].
  • Various motilin analogs were used to displace the motilin radioligand from the various tissue membranes [19].

Associations of MLN with chemical compounds

  • Human motilin receptors were sensitive to the NH(2)-terminal portion of the motilin molecule, but comparison with rabbit showed that both species had specific affinities for various motilin analogs [i.e., Mot-(1-9), Mot-(1-12), Mot-(1-12) (CH(2)NH)(10-11), and erythromycin] [19].
  • The response to motilin persisted in Ca(2+)-free solution (22.8+/-14.7%), was not affected by nifedipine (44+/-11%) but was abolished by incubation with thapsigargin (0+/-0%) [17].
  • Neither ryanodine, nor a previous stimulation with caffeine (0+/-0%) in Ca(2+)-free Krebs, nor both could block the response to motilin (28, 32.0+/-5.7, 41.3+/-6.1%, respectively) [17].
  • METHODS: Cytosolic Ca(2+) fluxes were monitored on a confocal microscope in cells loaded with Indo-1 and stimulated with motilin under various conditions [17].
  • The aborally decreasing gradient in response to motilin, known to exist in adult rabbits, was already present at day 8 (maximum contractile responses expressed as a percent of the maximal response to acetylcholine were 77% +/- 9%, 34% +/- 10%, and 25% +/- 8% for duodenal, jejunal, and ileal strips, respectively) [20].

Enzymatic interactions of MLN

  • AChE activity dropped from 21.6 mU/mg (nmol of the substrate hydrolysed per minute and per milligram protein) in NLN to 3.8 mU/mg in MLN (p < 0.001), while BuChE activity (3.6 mU/mg) was little affected [21].

Regulatory relationships of MLN

  • Motilin receptors obtained from synaptosomes or muscular plasma membranes of human antrum expressed different affinity for two motilin-receptor agonists, Mot-(1-12) and Mot-(1-12) (CH(2)NH)(10-11), suggesting that they correspond to specific receptor subtypes [19].
  • Subsequent experiments demonstrated that concentrations of synthetic motilin as low as 10(-9) M could significantly stimulate GH release [22].
  • A bolus of 100 mug and a subsequent 15-min infusion of 15 mug per min of somatostatin suppressed the fasting motilin level by 50% [23].
  • These data suggest that both motilin and OHM-11526 activate and ICaL in human and canine jejunal circular smooth muscle cells through a G protein-coupled mechanism [24].

Other interactions of MLN


Analytical, diagnostic and therapeutic context of MLN


  1. Motilin and motilin receptors: characterization and functional significance. Depoortere, I. Verh. K. Acad. Geneeskd. Belg. (2001) [Pubmed]
  2. Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomised, double blind, placebo controlled trial. Talley, N.J., Verlinden, M., Geenen, D.J., Hogan, R.B., Riff, D., McCallum, R.W., Mack, R.J. Gut (2001) [Pubmed]
  3. Failure of a motilin receptor agonist (ABT-229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric emptying: a randomized double-blind placebo-controlled trial. Talley, N.J., Verlinden, M., Snape, W., Beker, J.A., Ducrotte, P., Dettmer, A., Brinkhoff, H., Eaker, E., Ohning, G., Miner, P.B., Mathias, J.R., Fumagalli, I., Staessen, D., Mack, R.J. Aliment. Pharmacol. Ther. (2000) [Pubmed]
  4. The erythromycin derivative EM-523 is a potent motilin agonist in man and in rabbit. Depoortere, I., Peeters, T.L., Vantrappen, G. Peptides (1990) [Pubmed]
  5. Erythromycin effects on gastric emptying, antral motility and plasma motilin and pancreatic polypeptide concentrations in anorexia nervosa. Stacher, G., Peeters, T.L., Bergmann, H., Wiesnagrotzki, S., Schneider, C., Granser-Vacariu, G.V., Gaupmann, G., Kugi, A. Gut (1993) [Pubmed]
  6. Effect of octreotide on intestinal motility and bacterial overgrowth in scleroderma. Soudah, H.C., Hasler, W.L., Owyang, C. N. Engl. J. Med. (1991) [Pubmed]
  7. Receptor for motilin identified in the human gastrointestinal system. Feighner, S.D., Tan, C.P., McKee, K.K., Palyha, O.C., Hreniuk, D.L., Pong, S.S., Austin, C.P., Figueroa, D., MacNeil, D., Cascieri, M.A., Nargund, R., Bakshi, R., Abramovitz, M., Stocco, R., Kargman, S., O'Neill, G., Van Der Ploeg, L.H., Evans, J., Patchett, A.A., Smith, R.G., Howard, A.D. Science (1999) [Pubmed]
  8. Erythromycin intravenous bolus infusion in acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Frossard, J.L., Spahr, L., Queneau, P.E., Giostra, E., Burckhardt, B., Ory, G., De Saussure, P., Armenian, B., De Peyer, R., Hadengue, A. Gastroenterology (2002) [Pubmed]
  9. Dose-dependent stimulation of gallbladder contraction by intravenous erythromycin in man. Catnach, S.M., Ballinger, A.B., Law, P.A., Nellans, H., Fairclough, P.D. Aliment. Pharmacol. Ther. (1993) [Pubmed]
  10. Correlation between the cytotoxicity of melphalan and DNA crosslinks as detected by the ethidium bromide fluorescence assay in the F1 variant of B16 melanoma cells. Garcia, S.T., McQuillan, A., Panasci, L. Biochem. Pharmacol. (1988) [Pubmed]
  11. Plasma motilin concentration and interdigestive migrating motor complex in diabetic gastroparesis: effect of metoclopramide. Achem-Karam, S.R., Funakoshi, A., Vinik, A.I., Owyang, C. Gastroenterology (1985) [Pubmed]
  12. 5-hydroxytryptamine-3 receptors are involved in the initiation of gastric phase-3 motor activity in humans. Wilmer, A., Tack, J., Coremans, G., Janssens, J., Peeters, T., Vantrappen, G. Gastroenterology (1993) [Pubmed]
  13. Effect of octreotide on fasting gall bladder emptying, antroduodenal motility, and motilin release in acromegaly. Stolk, M.F., van Erpecum, K.J., Koppeschaar, H.P., Samsom, M., Smout, A.J., Akkermans, L.M., Peeters, T.L., vanBerge-Henegouwen, G.P. Gut (1995) [Pubmed]
  14. The motilin gene: subregional localisation, tissue expression, DNA polymorphisms and exclusion as a candidate gene for the HLA-associated immotile cilia syndrome. Gasparini, P., Grifa, A., Savasta, S., Merlo, I., Bisceglia, L., Totaro, A., Zelante, L. Hum. Genet. (1994) [Pubmed]
  15. Exon-intron organization, expression, and chromosomal localization of the human motilin gene. Yano, H., Seino, Y., Fujita, J., Yamada, Y., Inagaki, N., Takeda, J., Bell, G.I., Eddy, R.L., Fan, Y.S., Byers, M.G. FEBS Lett. (1989) [Pubmed]
  16. Plasma motilin in untreated celiac disease. Sjölund, K., Ekman, R. Peptides (2003) [Pubmed]
  17. Demonstration of a functional motilin receptor in TE671 cells from human cerebellum. Thielemans, L., Depoortere, I., Van Assche, G., Bender, E., Peeters, T.L. Brain Res. (2001) [Pubmed]
  18. Characterization of agonist-induced motilin receptor trafficking and its implications for tachyphylaxis. Lamian, V., Rich, A., Ma, Z., Li, J., Seethala, R., Gordon, D., Dubaquie, Y. Mol. Pharmacol. (2006) [Pubmed]
  19. Motilin receptors in the human antrum. Miller, P., Roy, A., St-Pierre, S., Dagenais, M., Lapointe, R., Poitras, P. Am. J. Physiol. Gastrointest. Liver Physiol. (2000) [Pubmed]
  20. Development of motilin receptors and of motilin- and erythromycin-induced contractility in rabbits. Depoortere, I., Peeters, T.L., Vantrappen, G. Gastroenterology (1990) [Pubmed]
  21. Breast cancer metastasis alters acetylcholinesterase activity and the composition of enzyme forms in axillary lymph nodes. Ruiz-Espejo, F., Cabezas-Herrera, J., Illana, J., Campoy, F.J., Muñoz-Delgado, E., Vidal, C.J. Breast Cancer Res. Treat. (2003) [Pubmed]
  22. Motilin: a novel growth hormone releasing agent. Samson, W.K., Lumpkin, M.D., Nilaver, G., McCann, S.M. Brain Res. Bull. (1984) [Pubmed]
  23. Pharmacokinetics of motilin in man. Mitznegg, P., Bloom, S.R., Domschke, W., Domschke, S., Wuensch, E., Demling, L. Gastroenterology (1977) [Pubmed]
  24. Motilin and OHM-11526 activate a calcium current in human and canine jejunal circular smooth muscle. Farrugia, G., Macielag, M.J., Peeters, T.L., Sarr, M.G., Galdes, A., Szurszewski, J.H. Am. J. Physiol. (1997) [Pubmed]
  25. Molecular characterization and distribution of motilin family receptors in the human gastrointestinal tract. Takeshita, E., Matsuura, B., Dong, M., Miller, L.J., Matsui, H., Onji, M. J. Gastroenterol. (2006) [Pubmed]
  26. Molecular heterogeneity of human motilinlike immunoreactivity explained by the processing of prepromotilin. Dea, D., Boileau, G., Poitras, P., Lahaie, R.G. Gastroenterology (1989) [Pubmed]
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